4- ferf-Butylcyclohexanone, reduction

This mixture is available from Aldrich Chemical Company, Inc. The checkers used a 7 93 mixture of the cis- and traws isomers, prepared by lithium aluminum hydride [Aluminate(l —), tetrahydro-, lithium, (T-4)-] reduction of 4-ferf-butylcyclohexanone and recrystallization of the crude product. The ketone was purchased from Aldrich Chemical Company, Inc. 

Rehydrated Mg/Al-OH catalysts have been found to be inactive in the MPV reduction of 4-ferf-butylcyclohexanone by isopropanol, whereas the bifunctional character of the Mg(Al)0 mixed oxides made them highly active in this reaction. The aluminium alkoxidc intermediate of the MPV reaction indeed involves a cooperation between basic and acidic sites. On mixed oxides, the abstraction of a proton from isopropanol on O2 sites gives isopropoxide anions, which are then stabilized on Al3+ and form intermediates with the aldehyde. The high activity of mixed oxide comes from the synergetic effect of strong Lewis basicity and mild acidity. 

Lithium tri-sec-butylborohydride, also known as L-selectride, is a metal hydride reagent that contains three sec-butyl groups bonded to boron. When this reagent is used to reduce cyclic ketones, one stereoisomer often predominates as product. Explain why the reduction of 4-ferf-butylcyclohexanone with L-selectride forms the cis alcohol as the major product. 

Hydroxymethyhtion of ketones. A ketone can be converted into the a-hydroxy-methyl derivative in two. steps acylation with ethyl formate, followed by aluminum hydride reduction. The sequence is illustrated for the conversion of 4-rerr-butylcyclo-hcxanone(l) inlo 2-hydroxymelhyl-4-ferf-butylcyclohexanone(3). 

On p. 1023, it was mentioned that electronic effects can play a part in determining which face of a carbon-carbon double bond is attacked. The same applies to additions to carbonyl groups. For example, in 5-substituted adamantanones (2) electron-withdrawing (-/) groups W cause the attack to come from the syn face, while electron-donating groups cause it to come from the anti face. In 5,6-disubstituted norborn-2-en-7-one systems, the carbonyl appears to tilt away from the 7i-bond, with reduction occurring from the more hindered face. An ab initio study of nucleophilic addition to 4-ferf-butylcyclohexanones attempted to predict 7i-facial selectivity in that system. ... 

The reduction of 4-ferf-butylcyclohexanone by LiAlH4 in THF at 0 °C affords a mixture of the tram- and ris-alcohols in 88.5 11.5 ratio (Table 1) [9]. The predominant attack takes place obviously from the axial direction as predicted above by the Cieplak model. This selectivity is expected to diminish when the ring carries an equatorial methyl group on C3 because it will (a) not introduce an element of steric interaction during the course of the nucleophilic addition, and (b) raise... 

Consult with your instructor before performing this experiment, in which you will determine the stereoselectivity of the reduction of 4-ferf-butylcyclohexanone with sodium borohydride. You might also be asked to use other hydride reducing agents and compare their stereoselectivities with that of sodium borohydride. Follow either... 

Purpose. The reduction of a ketone carbonyl to the corresponding alcohol is carried out using sodium borohydride, a commercially available metal-hydride reducing agent. The alcoholic reaction products are isolated by extraction techniques and purified by preparative gas chromatography. Cis and trans diastereomers are formed in the reduction of the 4-ferf-butylcyclohexanone. These diastereomeric products can be separated during the preparative GC isolation. The stereochemistry of the structures can be deduced, once the mixture is separated into its pure components, using either NMR or IR spectroscopy. 

Scheme 9.18. The results of the reduction of 4-ferf-butylcyclohexanone with lithium aluminum hydride (LiAlH4) in ether showing that the diequatorial product is preferred, although it is unclear if one face of the carbonyl is less encumbered than the other. (See Dauben, W. G. Fonken, G. I Noyce, D. S. J. Am. Chem. Soc. 1956, 78, 2579.)...

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